Purification as used herein encompasses the separation of an alcohol from other inert contaminants. Although a number of purification techniques for alcohols are known, the separation of a desired alcohol from closely related species is still difficult, especially on a large scale. As known, alcohols are valuable commodity chemicals with a wide range of uses, such as, for example, synthetic intermediates. Simple and versatile methods for purification that may be easily commercialized are badly needed.
One area of particular need is in the separation of chiral, nonracemic alcohols from their corresponding antipodal esters, the mixture of which may result from an enzymatic kinetic resolution. These enzymatic resolution methods typically include enzymatic hydrolysis, transesterification, or esterification. The separation of the antipodal ester from the racemic alcohol is particularly challenging because they are closely related species and the optical purity of product and/or substrate must be substantially maintained. The resulting separated compounds are of growing interest to the pharmaceutical, agricultural, and fragrance industries as optically active synthetic intermediates and building blocks.
There are several known methods for separating enzymatic resolution product mixtures. One known method is used for systems in which the chiral center resides in the carboxylate portion of the molecule (rather than the alcohol portion of the molecule), as shown in Figure I-1, below. In these systems, the enzymatic kinetic resolution (hydrolysis) results in a mixture of the unreacted ester and the corresponding antipodal carboxylic acid. Separation of the product carboxylic acid from the unreacted ester is usually accomplished simply by aqueous base extraction. For enzymatic resolution products where the chiral center resides in the alcohol portion of the molecule, (as shown in Figure I-2, below) separation is often accomplished by liquid chromatography. This technique, however, is generally only useful for small scale operations. Both reaction schemes are shown below in Figure I where R represents general organic substituents.